This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The incidence of type 2 diabetes in children has increased dramatically in the past decade. With earlier onset and thus longer duration of disease these children will have increased health care costs;they may also have more complications than someone diagnosed in middle age. There is little published experience on the best treatment to maintain normal glycemia and prevent complications in children with type 2 diabetes. This trial will determine which of 3 treatments is most effective in maintaining glycemic control. Although the trial will not be long enough to assess if there is a significant difference in complications between these 3 arms, surrogate markers associated with complications will be measured (e.g., lipid profile, C-reactive protein, microalbuminuria). This is a prospective, partially double-blinded, randomized clinical trial with 3 treatment arms: metformin alone, metformin plus intensive lifestyle treatment (behavior modification program). The primary endpoint is time to failure defined as hemoglobin A1c or =8% for 6 or more consecutive months. Subjects will be seen every 1 to 4 weeks during the 2-6 months of the runnin. After randomization, subjects will be seen every 2 months in the first year and every 3 months in subsequent years. In addition, subjects in the lifestyle arm will meet with a PAL (physical activity and nutrition leader) once a week for the first 6 months, every 2 weeks in the 2nd 6 months and monthly thereafter. Endpoint measurements will be done at randomization, 6 months, 24 months and end of study. Patients treated with metformin plus rosiglitizone will fail their primary therapy later than those on metformin alone. Failure is defined as Hemoglobin A1c8% for 6 months. Patients treated with metformin plus intensive lifestyle modification will fail later than those on metformin alone. SPECIFIC AIMS The primary objective of the TODAY trial is to compare the efficacy of the three treatment arms on time to treatment failure based on glycemic control. The secondary aims are to: compare and evaluate the safety of the three treatment arms;compae the effects of the three treatments on the pathophysiology of T2DM with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes;evaluate the influence of individual and family behaviors on treatment response;and compare the relative cost effectiveness of the three treatment arms. Type 2 Diabetes Mellitus (T2DM) has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. Over the last decade, the increase in the number of children and youth with T2DM has been labeled an "epidemic". Before the 1990's, it was rare for most pediatric centers to have patients with T2DM. By 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas, and by 1999, depending on geographic location, the range of percent of new cases due to T2DM was between 8-45% and disprpoortionately represented in minority populations. T2DM in children and youth, as in adults, is due to the combination of insulin resistance and relative beta cell ailure. It appears that there are a host of genetic and environmental risk factors for insulin resistance and limited beta cell reserve. The epidemic of pediatricT2DM is coincident with the rise in the number of children who are overweight or at risk for overweight and with a decrease in the physical activity pattern of youth. There has been a strong association between T2DM and the onset of puberty, a positive family history of T2DM, and elelements of the metabolic syndrome such as acanthosis nigricans and polycystic ovarian syndrome (PCOS). Despite the dramatic increase in the number of cases of T2DM in pediatric populations, there have been no published large-scale studies investigating the pathophysiology, treatment, and complications of these disorders in children and youth. The long-term complications and costs associated with T2DM make such studies imperative. Between 1997 and 2002, the estimated cost of diabetes with regard to direct medical cost increased from $44 billion to $92 billion, and the total cost icnreased from $98 billion to $132 billion. The vast majority of monies are spent on the long-term complications of this disorder. Since the long-term microvascular and cardiovascular complications relate to duration of diabetes and to control of glycemia, it could be hypothesized that the increasing number of children and youth diagnosed with T2DM, if not effectively treated, could dramatically add to the economic burden of this disease over the ensuing decades. The pharmacologic therapies for this study, which include using metformin alone and metformin in combination with rosiglitazone, were chosen because metformin is approved in pediatrics and because theoretically both of these agents improve insulin sensitivity. Additional agents were not chosen because the estimated number of patients available for recruitment would not support a trial with more than three arms. As the epidemic of T2DM in children and youth is relatively recent, there is little controlled evidence regarding the use of lifestyle modification to improve insulin sensitivity and glycemic control, induce wieght loss, or affect other outcome measures, such as dyslipideia and hypertension, in pediatric patients with T2DM.